CASE REPORT

Malignant Pleural Effusion in Acute Myeloid Leukemia

with Hepatitis B Virus Infection

C. Suharti, Santosa, Budi Setiawan

Department of Internal Medicine, Faculty of Medicine, Diponegoro University - dr. Kariadi Hospital. Semarang,
Indonesia.

Correspondence mail:
Division of Hematology-Medical Oncology, Department of Internal Medicine, Faculty of Medicine, Diponegoro
University - dr. Kariadi Hospital. Jl. Dr. Sutomo No.16, Semarang, Indonesia. email: catrin@indosat.net.id;
santosaiva@yahoo.com.

ABSTRAK
Efusi pleura dapat merupakan presentasi pertama dari keganasan hematologi. Di antara gangguan yang
paling umum adalah limfoma hodgkin dan limfoma non-hodgkin, dengan frekuensi 20 sampai 30%, terutama
jika terdapat keterlibatan mediastinum. Leukemia akut dan kronis jarang disertai dengan keterlibatan pleura.
Kami melaporkan wanita 46 tahun dengan sesak nafas yang progresif. Pemeriksaan fisik ditemukan dengan
efusi pleura kiri masif. Hitung darah lengkap menunjukkan anemia, trombositopenia, dan hitung leukosit normal
. Tes serologi virus menunjukkan HBsAg dan antiHBc total positif . Foto torak menunjukkan efusi pleura kiri.
Pemeriksaan sitologi cairan pleura didapatkan mieloblast. Aspirasi sumsum tulang, biopsi sumsum tulangi
dan analisis flowcytometry sesuai dengan leukemia myeloid akut tanpa maturasi (AML M0- klasifikasi FAB).

Kata kunci: leukemia myeloid akut, efusi pleura, infeksi.

ABSTRACT
Pleural effusions can be the first presentation of a hematologic malignancy. The most common disorders
with pleural effusion are Hodgkin and non-Hodgkin lymphoma with a frequency of 20 to 30%, especially if
mediastinal involvement. Acute and chronic leukemia are rarely accompanied by pleural involvement. We describe
a 46-year-old female with history of progressive dyspnoea. Physical examination was revealed massive left
pleural effusion. Complete blood count revealed anemia, trombositopenia and normal leucocyte count. Viral
serology test shown positive of HBsAg and total antiHBc. Chest X-ray revealed left pleural effusion. Pleural
fluid cytology was myeloblast consistent with acute myeloid leukemia (AML). Bone marrow aspiration smear,
bone marrow biopsy smear, and flow cytometry analysis were consistent with acute myeloid leukemia without
maturation (AML M0-FAB classification).

Key words: Acute myeloid leukemia, pleural effusion, infection.

INTRODUCTION is mediastinal involvement. Acute and chronic

Nearly all hematologic malignancies can
present with pleural effusions. The most
common disorders with plural effusin are
Hodgkin and non-Hodgkin lymphomas, with
a frequency of 20 to 30%, especially if there
leukemias, myelodysplastic syndromes, are
rarely accompanied by pleural involvement.
Furthermore, 10 to 30% of patients receiving
bone marrow transplantation develop pleural
effusions. In cases of hematologic pleural

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Santosa Acta Med Indones-Indones J Intern Med

effusions, should be carefully sought the drug

toxicity, underlying infectious, secondary Myeloblast
malignant or rarely autoimmune causes. In most
cases, the pleural fluid responds to treatment
for the primary disease and if there are clinical
worsening may necessitate pleurodesis.1,2
Myelosit
CASE ILLUSTRATION
A 46-year-old female was admitted to
hospital with history of progressive dyspnea for
two weeks. The onset of thes symptoms were
Figure 1. Bone marrow aspiration smear demonstrating
insidious, gradually progressive. There was myeloblast (HE, 400x)
history of fever, cough, weakness and loss of
appetite. Previously patient was hospitalized at
district hospital for 3 days.
Physical examination of patient revealed Myeloblast
tachypnoeia and tachycardia. The conjunctival
palpebrae were pale. There were echimosis
on the hand, enlarged of right inguinal lymph
nodes. There were no sternal tenderness and gum
hypertrophy. Chest examination showed severe
left side pleural effusion.
Complete blood count revealed haemoglobin:
6,60 g/dL, leukocyte : 4300/mm3, platelets :
10.000/mm3, hematocrit : 21,5%. The differential Figure 2. Bone marrow biopsy smear demonstrating
count were eosinophils 0% / basophils 0% / band myeloblast (HE, 400x)

neutrophils 0% / segmented neutrophils 41% /

lymphocytes 43% /Monocytes 2%. Peripheral
blood smear were erythroblast, myelocyte and Myeloblast
atypical mononuclear cells.
The biochemical analysis were glucose 149
mg/dL, urea 23 mg/dl, creatinine 0,88 mg/dl,
lactate dehydrogenase 221 U/L, uric acid 4,20
mg/dL, total protein 6,9 gr/dL, albumin 2,8
gr/dL, AST 48 U/L. The viral serology were
HBsAg positive, total anti HBc positive. The
prothrombine time (PPT) were 14,5” (control
13”) and activated partial thromboplastin time
(aPTT) was 31,4” (control 29,3”).
The anteroposterior and lateral chest X-ray Figure 3. Pleural fluid cytology showing myeloblast (cystopin,
400x)
were consistent with severe left side pleural
effusion. Abdomen ultrasonography showed no
hepatosplenomegaly. with acute myeloid leukemia (positive of CD34,
Bone marrow aspiration revealed 30% cyMPO and CD7). Pleural fluid culture showed
myeloblas ts, no maturation (M0-FAB Staphylococcus aureus (MSSA/Methicillin-
classification) (Figure 1). Bone marrow biopsy sensitive Staphylococcus aureus).
revealed >50% myeloblasts (Figure 2). Pleural The patient underwent theraupeutic
fluid cytology contained myeloblast. (Figure thoracentesis (1000 mL) with platelet transfusions
3). Flow cytometry analysis was consistent prophylaxis. Packed red cell (PRC) tansfusion

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Vol 47 • Number 2 • April 2015 Malignant pleural effusion in AML with hepatitis B virus infection
Figure 4. Anteroposterior chest X-ray showed masive left
sided pleural effusion
was given after bone marrow aspiration and
biopsy procedure. Broad spectrum antibiotic
(ceftriaxone 2 gr iv daily) was given for
community acquired pneumonia.
After four weeks therapy with thoracentesis
and ceftriaxon, there were clinical improvement.
The anteroposterior and lateral of chest X-ray
showed reduction of pleural pleural effusion
(Figure 4, Figure 5).
She was planned treatment with 3+7 AML
protocol (100 mg/m2 cytarabin for 7 days and
45 mg/m2 daunorubicin for 3 days). Prophylactic
antiviral therapy using lamivudine 100 mg p.o
qd for reduction of hepatitis B virus reactivation
following cytotoxic chemotherapy . She refused
chemoterapy because of economical reason and
dischrge home with supportive care.
DISCUSSION
The manifestation of pleural effusion can be
as a hematological malignancy or complication.
The possible pathogenesis are extramedullary
proliferation of occult leukemic clone or a
subclinical marrow relapse to extramedullary
sites. 1 The other causes of pleural effusion
were infections,disseminated of solid tumor, or
complications of treatment.2
The most common disorders are Hodgkin and
non-Hodgkin lymphomas, with a frequency of
20 to 30%, especially mediastinal involvement.
Acute and chronic leukemias are rarely
Figure 5. Anteroposterior chest X-ray four weeks after
therapy showed reduction of pleural effusion
accompanied by pleural involvement.1 Acute
myeloid leukemia with pleural effusion is a very
rare condition.2-5
The pleural infiltration of acute leukemias
is rarely diagnosed during life, it is a common
finding at autopsy. The presence of leukemic
infiltrates in other tissues in patients with acute
leukemias were found at autopsy in 10 of 15
patients who died of an unrelated cause, during
complete bone marrow remission.1 Besides
direct infiltration of leukemic cells in the pleura,
pleural effusion can be secondarily caused by
drug toxicity, underlying infections, secondary
malignant or rarely autoimmune causes in
hematologic malignancies.6
The presence of a pleural effusion in a
patient with a hematologic malignancy always
presents a diagnostic challenge. The effusion
is very small and thoracentesis is typically
considered. If fever is present, thoracentesis
is usually performed to exclude infection
and parapneumonic effusion or empyema.
Performing a thoracentesis has a high risk for
some patients with hematologic malignancies
because of coagulation abnormalities and
multiple medical comorbidities. The main
indication of thoracentesis was to detect an
infection, relieve dyspnea and cancer restaging.7,8
The pleural effusion in patients with acute
leukemia usually disappears after induction
chemotherapy. However, recurrence of pleural
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Santosa
exudates is almost inevitable if patients do
not achieve remission; they may present
with respiratory failure due to massive fluid
accumulation. In this circumstance, treatment
or palliation of pleural disease by intrapleural
chemotherapy or chemical sclerosis is impeded.1
Reactivation of HBV replication with
increase in serum HBV DNA and ALT levels
has been reported in 20% to 50% of hepatitis
B carriers undergoing immunosuppressive or
cancer chemotherapy. In most instances, the
hepatitis flares are asymptomatic, but icteric
flares, and even hepatic decompensation and
death have been observed. Clinical studies
including two controlled trials showed that
prophylactic therapy with lamivudine can reduce
the rate of HBV reactivation.9.10
HBsAg and antiHBc testing should be
performed in persons who have high risk of HBV
infection, prior to initiation of chemotherapy.
Prophylactic antiviral therapy should be
administered to hepatitis B carriers (regardless
of baseline serum HBV DNA levels) before
and during chemotherapy, and maintainance
treatment for 6 months.10-12
CONCLUSION
Pleural effusion can be a presentation of
hematology malignancy or a complication.
Pleural fluid should analysis for culture and
cytology in suspected patient with hematology
malignancy.
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